Dual specificity mitogen-activated protein kinase kinase 4

Details

Name
Dual specificity mitogen-activated protein kinase kinase 4
Synonyms
  • 2.7.12.2
  • c-Jun N-terminal kinase kinase 1
  • JNK-activating kinase 1
  • JNKK
  • JNKK1
  • MAP kinase kinase 4
  • MAPK/ERK kinase 4
  • MEK 4
  • MEK4
  • MKK4
  • PRKMK4
  • SAPK kinase 1
  • SAPK/ERK kinase 1
  • SAPKK-1
  • SAPKK1
  • SEK1
  • SERK1
  • SKK1
  • Stress-activated protein kinase kinase 1
Gene Name
MAP2K4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052665|Dual specificity mitogen-activated protein kinase kinase 4
MAAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKALKLNFANPPFKSTARFT
LNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDLKDLGEIGRGAYGSVNKMV
HKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPYIVQFYGALFREGDCWICMEL
MSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNHLKENLKIIHRDIKPSNILLDRS
GNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRQGYDVRSDVWSLGITLYEL
ATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEEREFSPSFINFVNLCLTKDESKRPKYKE
LLKHPFILMYEERAVEVACYVCKILDQMPATPSSPMYVD
Number of residues
399
Molecular Weight
44287.34
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / JUN kinase kinase activity / MAP kinase kinase activity / mitogen-activated protein kinase kinase kinase binding / protein kinase activity / protein serine kinase activity / protein threonine kinase activity / transmembrane receptor protein tyrosine kinase activity
Processes
activation of JUN kinase activity / activation of MAPK activity / apoptotic process / cell growth involved in cardiac muscle cell development / cellular response to mechanical stimulus / cellular response to sorbitol / Fc-epsilon receptor signaling pathway / JNK cascade / negative regulation of motor neuron apoptotic process / positive regulation of DNA replication / positive regulation of neuron apoptotic process / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of smooth muscle cell apoptotic process / response to wounding / signal transduction
Components
axon / cytosol / dendrite cytoplasm / nucleus / perikaryon
General Function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0052666|Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)
ATGGCGGCTCCGAGCCCGAGCGGCGGCGGCGGCTCCGGGGGCGGCAGCGGCAGCGGCACC
CCCGGCCCCGTAGGGTCCCCGGCGCCAGGCCACCCGGCCGTCAGCAGCATGCAGGGTAAA
CGCAAAGCACTGAAGTTGAATTTTGCAAATCCACCTTTCAAATCTACAGCAAGGTTTACT
CTGAATCCCAATCCTACAGGAGTTCAAAACCCACACATAGAGAGACTGAGAACACACAGC
ATTGAGTCATCAGGAAAACTGAAGATCTCCCCTGAACAACACTGGGATTTCACTGCAGAG
GACTTGAAAGACCTTGGAGAAATTGGACGAGGAGCTTATGGTTCTGTCAACAAAATGGTC
CACAAACCAAGTGGGCAAATAATGGCAGTTAAAAGAATTCGGTCAACAGTGGATGAAAAA
GAACAAAAACAACTTCTTATGGATTTGGATGTAGTAATGCGGAGTAGTGATTGCCCATAC
ATTGTTCAGTTTTATGGTGCACTCTTCAGAGAGGGTGACTGTTGGATCTGTATGGAACTC
ATGTCTACCTCGTTTGATAAGTTTTACAAATATGTATATAGTGTATTAGATGATGTTATT
CCAGAAGAAATTTTAGGCAAAATCACTTTAGCAACTGTGAAAGCACTAAACCACTTAAAA
GAAAACTTGAAAATTATTCACAGAGATATCAAACCTTCCAATATTCTTCTGGACAGAAGT
GGAAATATTAAGCTCTGTGACTTCGGCATCAGTGGACAGCTTGTGGACTCTATTGCCAAG
ACAAGAGATGCTGGCTGTAGGCCATACATGGCACCTGAAAGAATAGACCCAAGCGCATCA
CGACAAGGATATGATGTCCGCTCTGATGTCTGGAGTTTGGGGATCACATTGTATGAGTTG
GCCACAGGCCGATTTCCTTATCCAAAGTGGAATAGTGTATTTGATCAACTAACACAAGTC
GTGAAAGGAGATCCTCCGCAGCTGAGTAATTCTGAGGAAAGGGAATTCTCCCCGAGTTTC
ATCAACTTTGTCAACTTGTGCCTTACGAAGGATGAATCCAAAAGGCCAAAGTATAAAGAG
CTTCTGAAACATCCCTTTATTTTGATGTATGAAGAACGTGCCGTTGAGGTCGCATGCTAT
GTTTGTAAAATCCTGGATCAAATGCCAGCTACTCCCAGCTCTCCCATGTATGTCGATTGA
Chromosome Location
17
Locus
17p12
External Identifiers
ResourceLink
UniProtKB IDP45985
UniProtKB Entry NameMP2K4_HUMAN
HGNC IDHGNC:6844
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails